Viral expression of NE/PPE enhances anti-colorectal cancer efficacy of oncolytic adenovirus by promoting TAM M1 polarization to reverse insufficient effector memory/effector CD8+ T cell infiltration DOI Creative Commons
Shuo Wang,

Lingkai Kong,

Linpei Wang

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Март 14, 2025

Oncolytic adenoviruses are among the most widely utilized oncolytic viruses due to their notable anti-tumor and gene expression capabilities, modification of ADVs create armed remains a popular research direction. Nonetheless, immune suppression triggered by ADV targeted enhancements based on this limitation have been relatively unexplored. Flow cytometry was employed assess infiltration in tumor microenvironment following therapy. Targeted novel recombinant viruses, ADVNE ADVPPE, were designed, antitumor efficacy, safety, ability reshape evaluated both subcutaneous models mice vitro experiments. Immune cell depletion assays confirmed critical role macrophages. The impact HMGB1 macrophage polarization investigated using shRNA, qRT-PCR, ELISA, flow cytometry. Furthermore, importance TLR4 its downstream pathways validated through immunoprecipitation, Western blotting, homozygous knockout mice, inhibitors. We demonstrated that limits effector memory/effector CD8 + T cells (TEM/TE) within microenvironment. To address this, we leveraged strong capacity NE or PPE recruit TEM/TE constructing adenoviruses, with PPE. These induce pyroptosis colorectal cancer accompanied release HMGB1. binds surface macrophages, activating MyD88-NFκB-NLRP3 (ASC) pathway promoting M1 TAMs, thereby increasing enhancing efficacy. In summary, study presents development ADVPPE enhanced efficacy provides an in-depth exploration specific mechanisms. findings indicate promising clinical therapeutic prospects offer new insights for advancing adenovirus therapies.

Язык: Английский

Viral expression of NE/PPE enhances anti-colorectal cancer efficacy of oncolytic adenovirus by promoting TAM M1 polarization to reverse insufficient effector memory/effector CD8+ T cell infiltration DOI Creative Commons
Shuo Wang,

Lingkai Kong,

Linpei Wang

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Март 14, 2025

Oncolytic adenoviruses are among the most widely utilized oncolytic viruses due to their notable anti-tumor and gene expression capabilities, modification of ADVs create armed remains a popular research direction. Nonetheless, immune suppression triggered by ADV targeted enhancements based on this limitation have been relatively unexplored. Flow cytometry was employed assess infiltration in tumor microenvironment following therapy. Targeted novel recombinant viruses, ADVNE ADVPPE, were designed, antitumor efficacy, safety, ability reshape evaluated both subcutaneous models mice vitro experiments. Immune cell depletion assays confirmed critical role macrophages. The impact HMGB1 macrophage polarization investigated using shRNA, qRT-PCR, ELISA, flow cytometry. Furthermore, importance TLR4 its downstream pathways validated through immunoprecipitation, Western blotting, homozygous knockout mice, inhibitors. We demonstrated that limits effector memory/effector CD8 + T cells (TEM/TE) within microenvironment. To address this, we leveraged strong capacity NE or PPE recruit TEM/TE constructing adenoviruses, with PPE. These induce pyroptosis colorectal cancer accompanied release HMGB1. binds surface macrophages, activating MyD88-NFκB-NLRP3 (ASC) pathway promoting M1 TAMs, thereby increasing enhancing efficacy. In summary, study presents development ADVPPE enhanced efficacy provides an in-depth exploration specific mechanisms. findings indicate promising clinical therapeutic prospects offer new insights for advancing adenovirus therapies.

Язык: Английский

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